PHA 5127 Dose Optimization I Case Study I 1. Determine whether the elimination process in the graphs a-d is zero-order or first order. (Cp: Drug concentration in plasma) 05101520250246810Cp [µg/mL]Time (h)a) 12Zero-order (straight line) 1101000246810Cp [µg/mL]Time (h)b) 12First-order (straight line after semilogarithmic transformation of the y-axis)0123456789100246810Cp [µg/mL]Time (h)c) 12No Elimination 00.511.522.533.50246810ln Cp [µg/mL]Time (h)d) 12First-order (straight line after semilogarithmic transformation of the plasma concentrations) 2. 200 mg Drug A was administered to a female patient (60 kg) through IV bolus injection. The following plasma concentrations (Cp) were observed. time (h) Cp (µg/mL) 1 1.260 4 0.315 8 0.050 12 0.008 a) Plot Cp vs. time and determine the order of the elimination process0.0000.2000.4000.6000.8001.0001.2001.4000246810121Cp (µg/mL)time (h)Plasma concentration vs. time4Semilogarithmic transformation of the y-axis 0.0010.0100.1001.00010.0000 2 4 6 8 10 12 14Cp (µg/mL)time (h)Plasma concentration vs. time Plasma concentration vs. time profile is a straight line after semilogarithmic transformation. Thus, the elimination process is a first-order process. b) Determine ke and t1/2 (half life) time (h) Cp (µg/mL) ln Cp ( ) 0 2.000 0.6931 1 1.260 0.2310 4 0.315 ‐1.1552 8 0.050 ‐3.0036 12 0.008 ‐4.8520 1.1552 0.231041 0.4621 1 0.4621 1 /ln 21.5 ln ln ln11 0.2310 0.4621 1 0.6931 . 2.00 μc) Estimate the initial concentration C0 and the volume of distribution (Vd) 200 2.00 μ/ 100 d) Calculate AUC0-t(last)nd AUC0-∞ (Use trapezoidal rule) L) atime (h) Cp (µg/mL) AUC (µg*h/m0 2.000 1.63 1 1.260 2.36 4 0.315 0.73 8 0.050 0.11 12 0.008 AUC0-t(last) = (1.63 + 2.36 + 0.73 + 0.11) µg*h/mL = 4.83 µg*h/mL . μg/mL. / 0.0173 µg*h/mL 4.83 0.0173 μg h/mL 4.847 µg*h/mLe) Calculate AUC AUC 100% 4.83 h/mL4.847 μg h/mLμg 100% 99.65% f) Predict the plasma concentration after 6 hours6 2.00 μ. 0.125 μ 3. Define LADME and Pharmacokinetics ination in the body The ofile of a certain drug is dependent on the dosage form order elimination process, the half-life is dependent on the plasma concentration at time point 0 (C ) order elimination process, the half-life is dependent on the plasma concentration at time point 0 (C ) a high volume of distribution (Vd) have a narrow therapeutic window of perfusion limited distribution, the blood flow determines the rate of uptake of permeability limited distribution, the blood flow is not important for the rate of uptake LADME: Liberation, Absorption, Distribution, Metabolism, ElimPharmacokinetics: The time course of drug and metabolite concentration 4. TRUE (T) or FALSE (F) plasma concentration time prT F For a zero-0T F For a first-0T F Drugs withT F In the caseT F In the caseT
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